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Neural mechanisms of atrial arrhythmias


The past 5 years have seen great advances in the knowledge of neural mechanisms of atrial arrhythmogenesis. Direct autonomic nerve recordings demonstrate that simultaneous sympathovagal discharges and intrinsic cardiac nerve activities are common triggers of paroxysmal atrial tachycardia and atrial fibrillation. While activity of the autonomous nervous system (ANS) is crucial in triggering paroxysmal atrial fibrillation, a high incidence of sympathovagal co-activation at baseline is associated with a high vulnerability to pacing-induced sustained atrial fibrillation, suggesting that ANS has a role in the development of persistent atrial fibrillation. Modulation of ANS activity may constitute an important therapeutic strategy for the management of atrial tachyarrhythmias. Specifically, continuous, low-level stimulation of the left cervical vagus nerve effectively suppresses atrial tachyarrhythmias by reducing the nerve activity of the stellate ganglion. Clinically, compared with pulmonary vein isolation alone, the addition of ablation of intrinsic cardiac ganglia may confer better outcomes for patients with paroxysmal atrial fibrillation. These findings suggest that further investigation of the neural mechanisms of atrial arrhythmias might lead to better management of patients with atrial arrhythmias. In this article, we review the role of the ANS in the induction and maintenance of atrial arrhythmias and the role of neural modulation as a treatment strategy for atrial arrhythmias.

Key Points

  • Simultaneous sympathovagal discharges contribute to development and maintenance of atrial arrhythmias, as they increase calcium transient, trigger spontaneous calcium release from the sarcoplasmic reticulum, and shorten atrial action potentials

  • Direct nerve recordings in ambulatory animals have shown that paroxysmal atrial tachyarrhythmias are usually preceded by simultaneous sympathetic and vagal discharges and are invariably triggered by intrinsic cardiac nerve activities

  • Studies in ambulatory dogs have shown that cardiac nerve activities are also important in sustained atrial fibrillation

  • Novel strategies, including neural ablation and neural stimulation, can reduce arrhythmogenic nerve activities, but warrant further study before they can be widely applied in clinical settings

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Figure 1: Autonomic innervation of the heart.
Figure 2: The autonomic nervous system and paroxysmal atrial tachyarrhythmias.
Figure 3: ANS and persistent atrial fibrillation.
Figure 4: LL-VNS and nerve activity of the left stellate ganglion.


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This study was supported in part by NIH Grants P01HL78931, R01HL78932, R01HL71140, R21HL106554, a Heart Rhythm Society Fellowship in Cardiac Pacing and Electrophysiology (M. J. Shen) and a Medtronic-Zipes Endowment (P.-S. Chen).

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All authors researched data and wrote the article, contributed substantially to the discussion of content, and reviewed and edited the manuscript before submission.

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Correspondence to Peng-Sheng Chen.

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Shen, M., Choi, EK., Tan, A. et al. Neural mechanisms of atrial arrhythmias. Nat Rev Cardiol 9, 30–39 (2012).

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